ArticlePsychopharmacology2026
TM5441, a PAI-1 inhibitor, attenuates chronic stress-induced anxio-depressive-like behaviors by restoring the hippocampal PAI-1/tPA/BDNF axis.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
rationaleChronic unpredictable mild stress (CUMS) is a validated model of anxiety- and depression-like disorders and is associated with impaired neuroplasticity. Dysregulation of the plasminogen activator system, particularly elevated plasminogen activator inhibitor-1 (PAI-1), may disrupt tissue plasminogen activator (tPA)-dependent brain-derived neurotrophic factor (BDNF) signaling and contribute to stress-induced behavioral deficits. However, the therapeutic relevance of PAI-1 inhibition in mood disorders remains poorly defined.
aimThis study examined whether pharmacological inhibition of PAI-1 using TM5441 could alleviate CUMS-induced anxiety- and depression-like behaviors by modulating the hippocampal PAI-1/tPA/BDNF axis.
methodsMale and female C57BL/6 mice were exposed to CUMS for 3 weeks. TM5441, a selective SERPINE1 (PAI-1) inhibitor, was administered intraperitoneally (5 mg/kg) 20 min before behavioral testing, based on established efficacy and safety. Control mice received the vehicle (DMSO diluted in saline). Anxiety- and depression-like behaviors were assessed using the elevated plus maze, open field, sucrose preference, tail suspension, and forced swim tests. Hippocampal PAI-1, tPA, and BDNF levels were quantified, and correlations with behavioral outcomes were analyzed.
resultsTM5441 reversed CUMS-induced anxiety-like behaviors and depression-like responses. At the molecular level, TM5441 normalized stress-induced elevations in hippocampal PAI-1, restored tPA expression, and increased BDNF levels. Significant correlations were observed between PAI-1, tPA, and BDNF, as well as between hippocampal molecular markers and behavioral measures.
conclusionPAI-1 inhibition by TM5441 alleviates stress-induced behavioral deficits by restoring hippocampal tPA/BDNF signaling, highlighting the PAI-1/tPA axis as a promising therapeutic target for stress-related mood disorders.
Indexed as
Identifiers
42171693What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.